Targeting virus-specific CD8+T cells for treatment of chronic viral hepatitis: from bench to bedside

IntroductionMore than 350 million people worldwide live with chronic viral hepatitis and are thus at risk for severe complications like liver cirrhosis and hepatocellular carcinoma (HCC). To meet the goals of the World Health Organization (WHO) global hepatitis strategy, there is an urgent need for new immunotherapeutic approaches. These are particularly required for chronic hepatitis B virus infection and - B/D coinfection.Areas coveredThis review summarizes data on mechanisms of CD8+ T cells failure in chronic hepatitis B, D, C and E virus infection. The relative contribution of the different concepts (viral escape, CD8+ T cell exhaustion, defective priming) will be discussed. On this basis, examples for future therapeutic approaches targeting virus-specific CD8+ T cells for the individual hepatitis viruses will be discussedExpert opinionImmunotherapeutic approaches targeting virus-specific CD8+ T cells have the potential to change clinical practice, especially in chronic hepatitis B virus infection. Further clinical development, however, requires a more detailed understanding of T cell immunology in chronic viral hepatitis. Some important conceptual questions remain to be addressed, e.g. regarding heterogeneity of exhausted virus-specific CD8+ T cells. Chronic viral hepatitis is a global health issue with an urgent need for new therapeutic approaches. Cytotoxic T killer cells (virus-specific CD8+ T cells) are key players in mediating control of viral hepatitis, and chronic infection is associated with dysfunction of these cells. Therefore, reconstitution of virus-specific CD8+ T cells by immunotherapy is an interesting therapeutic approach for chronic viral hepatitis. In this review, we will compare data on different mechanisms contributing to CD8+ T cell dysfunction in chronic hepatitis B, C, D, and E virus infection, respectively. Furthermore, preclinical and clinical studies for the individual hepatitis viruses will be discussed.